A20 INHIBITS NF-KAPPA-B ACTIVATION INDEPENDENTLY OF BINDING TO 14-3-3-PROTEINS

The A20 protein, which belongs to a class of Cys(2)/Cys(2) zinc finger proteins, has been characterized as an inhibitor of NF-kappa B activa tion. In order to clarify its molecular mechanism of action, the yeast two-hybrid system was used to screen for interacting proteins. We rep ort that different isoforms of 14-3-3 proteins, viz. eta and zeta, are able to bind A20, involving the 14-3-3-binding motif RSKSDP located b etween zinc fingers 3 and 4. However, A20 mutants that no longer assoc iated with 14-3-3 proteins could still fully inhibit NF-kappa B activa tion induced by tumor necrosis factor, interleukin-1 beta or phorbol 1 2-myristate 13-acetate, thus excluding a crucial role for 14-3-3 inter action in this A20 function. (C) 1997 Academic Press.